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allergy and hypersensitivity reactions

Hypersensitivity reactions - the Gell & Coombs classification

Type I - Immediate (Anaphylactic)

priming event:

  • antigen binds to Antigen presenting Cell (APC) ⇒ activates T Helper cell ⇒ IL-4 production ⇒ B IgE type ⇒ IgE production

acute event:

  • mast cell degranulation due to either:
    • IgE from priming event binds antigen complex
      • it appears a protein, neuritin, prevents the over-production of IgE and thus allergies, anaphylaxis, asthma and many auto-immune conditions could be the result of a deficiency of neuritin according to researchers at the Australian National University (ANU) in 2021
    • direct degranulation via C3alpha/C5alpha, morphine, codeine;
  • ⇒ immediate granule release (~20 min)
    • histamine, etc
    • ⇒ H1 effector ⇒ increased permeability; urticaria; asthma;
    • ⇒ H2 feedback ⇒ down-regulation
    • ⇒ decreased mast cell degranulation
    • ⇒ decreased PMNL activity, etc;
    • ⇒ activation phospholipase A2 (slow ~8 hrs, inhib. by NSAID/steroids)
    • ⇒ PG, thromboxane, SRS-A, leukotriene production;

Type II - Cytotoxic

  • Ab + Ag (assoc. with or part of a cell/tissue) ⇒ complement activation
    • ⇒ lytic action on cell memb. via complement/effector cell products
  • eg. Goodpasture's disease; Rh isoimmunisation disease of pregnancy; autoimmune haemolyticanaemia;
  • eg. myasthenia gravis (not lytic though only Ig bind Ach receptors)

Type III - Immune complex mediated (IgG/IgM)

  • Ab-Ag complexes in circulation in ratio 1-2:1 may cause deposition onto cell membranes activating complement 
    • ⇒ local inflammation including urticaria with joint effusions
  • eg. serum sickness (such as due to 1-2wks after taking cefaclor)
  • if Ab»Ag, then v.large complexes which are taken up by phagocytes & hence no serum sickness;

Type IV - Delayed type (DTH)

  • cell mediated

contact HS (max. reaction time 48-72 hours)

  • hapten on/in epidermis activates Langerhan's ⇒ LN T cells
    • ⇒ local mainly epidermal inflammatory response
      • ⇒ spongiosis/blisters with initially lymphocytic infiltration & later macrophages;
  • eg. poison oak; nickel;

Tuberculin-type HS (max. reaction time 48-72 hours)

  • soluble transient hapten in dermis activates macrophages
    • ⇒ dermal response ⇒ papule with monocytic infiltrate & some macrophages;

Granulomatous HS (max. reaction time > 14 days)

  • continuous Ag stimulation ⇒ macrophage activation;
allergy.txt · Last modified: 2022/04/15 23:39 by wh

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